From the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center (Drs Stanford, Weiss, Voigt, Daling, and Rossing, and Ms Habel), and Department of Epidemiology, School of Public Health and Community Medicine, University of Washington (Drs Stanford, Weiss, Daling, and Rossing, and Ms Habel), Seattle, Wash.

Objective.—To determine the risk of breast cancer in relation to the use of combined estrogen and progestin hormone replacement therapy (HRT).

Design.—A population-based case-control study.

Setting.—The general female population of King County in western Washington State.

Participants.—Middle-aged (50 to 64 years) women, including 537 patients with incident primary breast cancer diagnosed between January 1,1988, and June 30, 1990, who were ascertained through the Seattle—Puget Sound Surveillance, Epidemiology, and End Results cancer registry and 492 randomly selected control women without a history of breast cancer.

Main Outcome Measure.—Breast cancer risk in relation to use of menopausal hormones.

Results.—Menopausal hormones of some type had been used by 57.6% of breast cancer cases and 61.0% of comparison women. The women who had ever taken combined estrogen-progestin HRT, representing 21.5% of cases and 21.3% of controls, were not at increased risk of breast cancer (relative odds [RO]=0.9; 95% confidence interval [CI], 0.7 to 1.3). Compared with nonusers of menopausal hormones, those who used estrogen-progestin HRT for 8 or more years had, if anything, a reduced risk of breast cancer (RO=0.4; 95% CI, 0.2 to 1.0).

Conclusions.—On the whole, the use of estrogen with progestin HRT does not appear to be associated with an increased risk of breast cancer in middle-aged women. Nonetheless, since the use of combined estrogen-progestin HRT has only recently become prevalent, future investigations must assess whether breast cancer incidence is altered many years after estrogen-progestin HRT has been initiated, particularly among long-term users.(JAMA. 1995;274:137-142)